General Information:

Id: 466
Diseases: Parkinson disease
Drosophila melanogaster
BTO:0000142 brain
article
Reference: Tain LS et al.(2009) Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss Nat. Neurosci. 12: 1129-1135 [PMID: 19684592]

Interaction Information:

Comment Overexpression of 4E-BP in Pink1 and park mutants was capable of significantly suppressing dopaminergic neuron loss. This indicates that 4E-BP mediates a protective mechanism that is sufficient to prevent the pathologic consequence of loss of parkin or Pink1.
Formal Description
Interaction-ID: 2113

gene/protein

EIF4EBP1

decreases_activity of

process

neuron death

if 4E-BP is overexpressed in parkin mutant
Comment Overexpression of 4E-BP in Pink1 and park mutants was capable of significantly suppressing dopaminergic neuron loss. This indicates that 4E-BP mediates a protective mechanism that is sufficient to prevent the pathologic consequence of loss of parkin or Pink1.
Formal Description
Interaction-ID: 2116

gene/protein

EIF4EBP1

decreases_activity of

process

neuron death

if 4E-BP is overexpressed in Pink1 mutant
Comment Akt1/TOR signaling pathway represses 4E-BP activity. Rapamycin did not prevent neurodegeneration in 4e-BP mutants suggesting that effects of rapamycin are mediated by 4E-BP.
Formal Description
Interaction-ID: 2119

process

TOR signaling

decreases_activity of

gene/protein

EIF4EBP1

Comment 4E-BP is negatively regulated via phosphorylation by TOR, which can be inhibited by exposure to rapamycin.
Formal Description
Interaction-ID: 2121

process

TOR signaling

increases_phosphorylation of

gene/protein

EIF4EBP1

Comment 4E-BP is negatively regulated via phosphorylation by TOR, which can be inhibited by exposure to rapamycin.
Formal Description
Interaction-ID: 2122

drug/chemical compound

Rapamycin

decreases_activity of

process

TOR signaling

Comment Addition of Rapamycin suppressed neuron degeneration in parkin and Pink1 mutants. Rapamycin did not prevent neurodegeneration in 4e-BP mutants suggesting that effects of rapamycin are mediated by 4E-BP.
Formal Description
Interaction-ID: 2124

drug/chemical compound

Rapamycin

decreases_activity of

process

neuron death

Comment Homozygous Lrrk(e03680) loss-of-function mutations cause a decrease in the amount of phosphorylated 4E-BP compared with wild type.
Formal Description
Interaction-ID: 2125

gene/protein

LRRK2

increases_phosphorylation of

gene/protein

EIF4EBP1

Comment Thor and park double mutants were essentially lethal. This lethality could be rescued by targeted expression of 4E-BP.
Formal Description
Interaction-ID: 4007

gene/protein

PARK2

decreases_activity of

process

neuron death

Comment Thor and park double mutants were essentially lethal. This lethality could be rescued by targeted expression of 4E-BP.
Formal Description
Interaction-ID: 4008

gene/protein

EIF4EBP1

decreases_activity of

process

neuron death

in Thor and park double mutants
Comment 4E-BP overexpression suppresses park and Pink1 mutant phenotypes.
Formal Description
Interaction-ID: 4009

gene/protein

EIF4EBP1

decreases_activity of

gene/protein mutant

PARK2-mut

Comment 4E-BP overexpression suppresses park and Pink1 mutant phenotypes.
Formal Description
Interaction-ID: 4010

gene/protein

EIF4EBP1

decreases_activity of

gene/protein mutant

PINK1-mut

Comment There was a significant reduction in the level of hyper-phosphorylated 4E-BP in parkin and PINK1 mutants, and a concomitant increase in the proportion of active, non-phosphorylated 4E-BP.
Formal Description
Interaction-ID: 4034

gene/protein mutant

PINK1-mut

decreases_phosphorylation of

gene/protein

EIF4EBP1

Comment There was a significant reduction in the level of hyper-phosphorylated 4E-BP in parkin and PINK1 mutants, and a concomitant increase in the proportion of active, non-phosphorylated 4E-BP.
Formal Description
Interaction-ID: 4047

gene/protein mutant

PARK2-mut

decreases_phosphorylation of

gene/protein

EIF4EBP1

Comment In parkin/PINK1 mutants the Akt1/TOR signaling pathway that regulates 4E-BP activity and global protein translation is down-regulated typical of a stress response to promote protective mechanisms.
Formal Description
Interaction-ID: 4049

gene/protein mutant

PINK1-mut

decreases_activity of

process

TOR signaling

Comment In parkin/PINK1 mutants the Akt1/TOR signaling pathway that regulates 4E-BP activity and global protein translation is down-regulated typical of a stress response to promote protective mechanisms.
Formal Description
Interaction-ID: 4050

gene/protein mutant

PARK2-mut

decreases_activity of

process

TOR signaling